Atherosclerosis: Insights into Vascular Pathobiology and Outlook to Novel Treatments

Area of Science:

• Cardiovascular Biology
• Immunology
• Cellular Pathophysiology

Background:

• Atherosclerosis involves complex cellular interactions and inflammatory processes.
• Endothelial cells (ECs), macrophages, and vascular smooth muscle cells (VSMCs) are key players in atherogenesis.
• Understanding these cell types is crucial for developing effective treatments.

Purpose of the Study:

• To summarize the pathobiology of atherosclerosis.
• To review current and potential future therapeutic strategies.
• To spotlight the roles of ECs, macrophages, and VSMCs.

Main Methods:

• Review of current literature on atherosclerosis pathobiology.
• Analysis of cellular mechanisms involving ECs, macrophages, and VSMCs.
• Exploration of emerging therapeutic targets and approaches.

Main Results:

• Endothelial cell behavior is influenced by biomechanical forces via YAP/TAZ transcription factors.
• Vascular smooth muscle cell transdifferentiation contributes significantly to macrophage markers in plaques.
• Intra-plaque macrophages are activated via pattern recognition receptors and neutrophil extracellular traps (NETs).
• Single-cell RNA sequencing aids in characterizing ECs and macrophages.
• Adaptive immunity plays a critical role in the inflammatory cascade.

Conclusions:

• Targeting specific cellular pathways and immune responses offers promising therapeutic avenues.
• Future treatments may include vaccination, TRAF-STOPs, senolysis, and CD47 blockade.
• Further research into cellular mechanisms is vital for advancing atherosclerosis treatment.